NCT06546085

Extracellular Vesicles, Insulin Action, and Exercise

Extracellular Vesicles, Insulin Action, and Exercise on Vascular Function in Type 2 Diabetes

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Rutgers, The State University of New Jersey · Academic / Other
• Sex: All
• Age: 30 Years – 80 Years
• Healthy volunteers: Accepted

Summary

Extracellular vesicles (EVs) play a role in obesity-induced insulin resistance and likely impact the development of cardiovascular disease. However, little is known on how EVs affect vascular insulin action in people. The purpose of this study is to understand how EVs play a role in type 2 diabetes related cardiovascular disease. This research will also study if exercise can change how EVs impact blood flow and metabolic health. This study will contribute to designing precision medicine to treat/prevent cardiovascular disease in type 2 diabetes.

Detailed description

Insulin resistance is a key underlying factor promoting hyperglycemia and hypertension in people with type 2 diabetes (T2D), who have a 3-fold greater cardiovascular disease (CVD) risk when compared with healthy controls. Despite several therapeutic approaches that favor insulin sensitivity through a variety of purported mechanisms (e.g. weight loss, incretins, AMPK activation, reduction in bioactive lipids: DAG/ceramides, etc.), long-term progression of glucose deterioration occurs. This suggests adjunctive targets may be important to prevent/reverse T2D. Studies show that extracellular vesicles (EVs) obtained from plasma are involved in obesity-induced insulin resistance at levels of adipocytes, muscle, and liver. However, little is known how plasma EVs affect vascular insulin action in humans. This is of clinical relevance as EVs enhance the Framingham Risk Score, suggesting EVs are a unique factor promoting CVD. This proposal will fill this knowledge gap by conducting a translational study in 3 distinct groups of people separated by obesity and T2D. The investigators hypothesize that 1) insulin will promote EV uptake and modify insulin signaling in endothelial cells, 2) EVs from adults with T2D will impair vessel reactivity compared to controls; 3) insulin will alter circulating EV insulin signaling and cargo, and 4) exercise training will change EV uptake and cargo as well as EV mediated vascular reactivity to insulin as well as relate to improved vascular function in humans.

Conditions

• Type 2 Diabetes
• Obesity

Interventions

Type	Name	Description
BEHAVIORAL	Exercise	Supervised treadmill exercise at 85% VO2max, 3x/wk for 16 weeks. Exercise duration will be adjusted based on individual VO2-heart rate (HR) relationship so that \~400 kcals will be expended during each training session.

Timeline

• Start date: 2025-02-10
• Primary completion: 2029-01-01
• Completion: 2029-04-01
• First posted: 2024-08-09
• Last updated: 2026-01-23

Locations

3 sites across 1 country: United States